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Gene May Explain Sex-Switch Syndrome

By Reuters
Contributed by Claire-Louise Stafford & Jodie Miller

London
Febrary 21, 1998


British and Italian researchers yesterday said they had identified a gene they believe causes sex-reversal syndrome, in which people have the chromosomes of one sex but the physical attributes of the other.

Scientists had already suspected that the DAXI played a role in the troubling condition. Now they believe they have proof.

"The evidence we have strongly suggests that DAXI is the gene responsible for sex reversal syndrome. Just a simple duplication of the gene in a double dose apparently leads to sex reversal". Mr Robin Lovell-Badge, of the MRC National Institute for the Medical Research said.

DAXI lies on the X chromosome. When it duplicates it causes an individual who is genetically male to develop physically as a female. Another gene called Sry, on the Y chromosome, is the main sex gene that determines whether testes will develop in the embryo.

Mr. Lovell-Badge and researchers at the university of Pavia in Italy conducted experiments on transgenic mice to determine how DAXI and Sry work. The research offers new insight into how sex is determined and identifies the underlying cause of the disorder.

In a report published in the scientific journal Nature, they showed that the interaction of Sry and DAXI is vital in the early stages of sex-determination.

"We know that Sry is the gene critical for male development. If it isn’t there you get a female," Mr Lovell-Badge said. "DAXI and Sry act in the same pathway, (chain of events), but in a normal male Sry wins. The normal function of DAXI, we believe, is to ensure that secondary male genes are turned off. It’s an anti-male gene." In most female cases, those with sex reversal syndrome are not aware of it until puberty, when they fail to ovulate or have their menstrual cycle.

"They are women but they are not fertile," said Mr. Lovell-badge.

There are also individuals who are chromosomal females with XX chromosomes but who develop as males. Again the condition may not be evident until puberty.

The researchers’ work was limited to physical sex reversal, but Mr Lovell-Badge said that since DAXI was found in other parts of the embryo, including the brain, it could have an effect on sex specific behaviour. For example it might explain why some females feel trapped in a male body and vice versa.



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